Comprehensive Summary The pentafluorosulfanyl (SF5) group, characterized by its high electronegativity, lipophilicity and unique octahedral geometry, has the potential to modify the physicochemical properties of both pharmaceuticals and agrochemicals. Recently, pentafluorosulfanyl-containing compounds have garnered increasing attention, and big progress has been made in the development of novel synthetic strategies for these compounds. Central to these advancements is the exploration of synthesis and novel reaction of radical pentafluorosulfanylation reagents. This account provides an overview of the gas-reagent-free practical synthesis and new reaction of pentafluorosulfanyl chloride (SF5Cl) developed by our group.Key Scientists of SF5 Chemistry A partial list of the key scientists' main contributions to the development of pentafluorosulfanyl chemistry

Hygromycin A, a once-forgotten antibiotic first isolated in 1953, is recently rediscovered as a novel inhibitor of Lyme disease caused by Borrelia burgdorferi. Given the increasing resistance of gut microbes to antibiotic treatments, there is an urgent need for new therapies with novel mechanisms of action. The molecular architecture of hygromycin A, characterized by its fragmented structure, makes it an appealing platform for derivatization. In this study, it develops a latent functionality strategy to introduce the beta-hydroxy ketone motif into the sugar fragment via the 1,3-dipolar cycloaddition of furan. The facile epimerization at the C5 position enables a rapid access congeners of hygromycin A. Furthermore, glycosylation with phenol derivatives provides a versatile method for establishing the unique stereogenic center of the furanoside in this class of compounds.

Combining in vivo and in vitro approaches, we elucidated the phoslactomycin post-PKS tailoring pathway in S. platensis. Gene inactivation of pnT1-pnT7 revealed seven phoslactomycin derivatives (four novel). Two cytochrome P450s were identified: PnT3 (mediating dual-site, multistep C-8/C-25 oxidation) and PnT7 (catalyzing C-18 hydroxylation). Activity evaluation established essential C-9 phosphate and detrimental epsilon-lactone/C-3 malonyl effects. These findings bridge the gap in phoslactomycin modification, highlighting a versatile P450 PnT3, and provide SAR foundations for PP2A inhibitor design.

Difluoromethylene moiety has gained widespread applications in pharmaceuticals, agrochemicals, and materials owing to its augmented lipophilicity and being bioisosteric to ethereal oxygen. Possessing two orthogonal reactivity modes for bridging an electrophile and a radical acceptor to give gem-difluorides (R1-CF2-R2), the efficient difluoromethylene radical anion synthon (diFRAS) has been long sought after. In this work, we successfully utilize the readily available difluoromethyl phenyl sulfone (PhSO2CF2H) to couple with electrophiles and radical acceptors, thereby enabling PhSO2CF2H to serve as a novel diFRAS in organic synthesis. The generation of radicals (center dot CF2R) via visible light-promoted homolytic cleavage of C-S bonds in (phenylsulfonyl)difluoromethylated derivatives (PhSO2CF2R) is the linchpin in the diFRAS strategy to construct gem-difluorides (R1-CF2-R2) with structural complexity.

A chemodivergent mono- and double-dehydrosilylation (DHS) of arylalkenes with hydrosilanes has been realized by bipyridyl-phosphinite (PONN) and bipyridyl-phosphine (PCNN) supported cobalt complexes. A series of phosphinite-containing complexes (PONN)CoCl2 (Co1-Co5) with an O-linker between the P atom and the bipyridyl backbone were synthesized. Among them, the tBu-substituted complex ( tBuPONN)CoCl2 (Co4), with NaBEt3H as the activator, exhibits high catalytic efficiency and selectivity for the mono-DHS of arylalkenes with PhMeSiH2 to form (E)-vinylsilane, but it is barely active for the DHS reactions with sterically more hindered secondary hydrosilanes (e.g., Ph2SiH2) and tertiary hydrosilanes. In contrast, the phosphine variant ( tBuPCNN)CoCl2 (Co6) with a C-linker and phosphino-tBu substituents catalyzes selective double-DHS with PhMeSiH2, furnishing symmetric quaternary (E)-divinylsilanes with two vinyl groups attached to the same Si-center. Moreover, Co6 was found to be highly efficient for the mono-DHS of arylalkenes with various hindered secondary hydrosilanes (TOF up to 21,000 h-1 when using Ph2SiH2), while the iPr-substituted analog ( iPrPCNN)CoCl2 (Co7) proved effective and selective for the mono-DHS with bulky tertiary hydrosilanes. Thus, a combination of Co6-catalyzed mono-DHS with secondary hydrosilane and Co7-catalyzed mono-DHS with the resulting tertiary vinyl hydrosilane enables the sequential double-DHS, allowing for the synthesis of unsymmetric quaternary (E)-divinylsilanes from two different arylalkenes. The observation of Co(I) silyl and Co(III) bis(silyl) hydride complexes suggests that the DHS reactions probably proceed through a Co(I)/Co(III) redox process with a Co(III) bis(silyl) hydride species as the catalyst resting state.

Sterically congested alkenes-ubiquitous in pharmaceuticals and industrial intermediates-remain inaccessible to classical hydroformylation due to prohibitive steric strain in transition-metal catalysis. Here, we report a thiophenol-catalyzed radical hydroformylation that overcomes dual steric and electronic constraints through a synergistic system: bench-stable alpha-chloro N-methoxyphthalimides (formyl precursors) and a tailored thiophenol HAT catalyst. This metal-free strategy achieves unprecedented hydroformylation of unactivated, tri-, and tetrasubstituted alkenes-including electron-rich styrenes and aliphatic alkene systems-with high chemo- and regioselectivity. Key advances include: 1) the first hydroformylation of tetrasubstituted styrenes, delivering beta-aryl aldehydes with quaternary centers (up to 74% yield); 2) thiophenol lowers the HAT barrier by 8.3 kcal/mol to enable catalytic turnover under steric congestion. Mechanistic studies confirm a formyl radical pathway, while syngas (CO/H2) elimination establishes a safe, sustainable platform for synthesizing medicinally relevant motifs (e.g., oxime ethers) and industrial targets like Lilial derivatives.

Two hundred eight genetic mutations in SOD1 have been linked to amyotrophic lateral sclerosis (ALS). Of these, the G93A and D101N variants maintain much of their physiological function, closely resembling that of wild-type SOD1, and the SOD1-G93A transgenic mouse is the most extensively used mouse line in the study of ALS. In this study, we report two cryo-EM structures of amyloid fibrils formed by G93A and D101N mutants of SOD1 protein. These mutations give rise to amyloid fibrils with distinct structures compared to native SOD1 fibrils. The fibril core displays a serpentine configuration featuring four beta-strands, held together by two hydrophobic cavities and a salt bridge between Arg143 and Asp96 in the G93A fibril, and by a hydrophobic cavity and a salt bridge between Arg143 and Asp132 in the D101N fibril, demonstrating unique structural features for each mutant. Moreover, our results show that G93A fibrils are significantly more toxic than those formed by D101N, which do not show a marked increase in toxicity compared to wild-type SOD1 fibrils. This study sheds light on the structural mechanisms through which SOD1 mutants aggregate and induce cytotoxicity in ALS.